Fibrinogen is a glycoprotein involved in hemostasis, and has been implicated in numerous aspects of vascular disease including atherosclerosis and stroke. Its plasmin degradation products possess various biological activities which may be important in the development of acute respiratory distress. In spite of the biological importance of fibrinogen we know virtually nothing about its detailed tertiary structure. Such information could be provided by high resolution X-ray data; however this appears remote since native fibrinogen has not been crystallized. In lieu of the crystallographic data, we propose to obtain a picture of the topology of fibrinogen by determining surface oriented tyrosines which are iodinated by lactoperoxidase. The broad aim of this proposal is to determine the surface oriented tyrosines in fibrinogen, fibrin monomers and fibrin polymers and to determine the location of the high affinity calcium binding sites in fibrinogen. The objectives are to define the topology of the fibrinogen molecule, identify the regions of conformational change on conversion of fibrinogen to fibrin and to locate the polymerization sites on fibrin monomers. the iodinated fibrinogen or fibrin will be analyzed for the distribution of iodine in specific tyrosines by fragmentation with cyanogen bromide and isolation of N-DSK and Hi2-DSK and by plasmin digestion and isolation of fragments D and E. Second, N-DSK, E and S will be reduced, alkylated and the chains of each purified. Chains of D will be treated with cyanogen bromide and the fragments purified. Specific iodinated tyrosines will be identified by peptide mapping of tryptic digests of each fragment of chain followed by identificaiion of iodinated peptides by amino terminal analysis and amino acid composition.